Results show that VIP treatment inhibits caspase-3 activation, but does not enhance the expression and activation of ERK, Akt, c-fos, egr1, and BDNF as PACAP treatment do, which suggests that although activation of VPAC1R/VPAC2R induces protection against mHtt, the activation of PAC1R is required to activate pro-survival and neurotrophic mechanisms contributing to the long lasting functionality of striatal cells in HD models. Here, CASP3 is linked to Huntington disease.